| Project/Area Number |
13480262
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Neurochemistry/Neuropharmacology
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| Research Institution | National Center of Neurology and Psychiatry (NCNP) |
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Principal Investigator |
WADA Keiji National Center of Neurology and Psychiatry, National Institute of Neuroscience, Department of Degenerative Neurological Diseases, Director, 疾病研究第四部, 部長 (70250222)
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| Co-Investigator(Kenkyū-buntansha) |
NODA Mami Kyushu University, Graduate School of Pharmaceutical Sciences, Associate Professor, 大学院・薬学研究院, 助教授 (80127985)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2002: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2001: ¥7,800,000 (Direct Cost: ¥7,800,000)
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| Keywords | ubiquitin / neurodegeneration / mouse / protein degradation / neuron / neurotransmission / neuroregeneration / synapse / 幹細胞 / 神経軸索 / パーキンソン病 / 神経細胞死 |
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| Research Abstract |
We previously identified that ubiquitin C-terminal hydrolase L1 (UCH-L1) was not expressed in the gracile axonal dystrophy (gad) mouse. The gad mouse is pathologically characterized by dying-back type of axonal degeneration, and thus the mutant appears to be a suitable model for investigating the relationship between the ubiquitin system and synapes. In this study, we aimed to elucidate the physiological and pathophysiological roles of UCH-L1 in the maintenance of synaptic structure and function. We first identified that UCH-L1 unexpectedly bound to and stabilized monoubiquitin in neurons. In the stablization, hydrolase activity of UCH-L1 was not required. In the gad mouse, monoubiquitin level was decreased. These results suggest that UCH-L1 may function in multiple ways : as a hydrolase and as a ubiquitin-binding protein in vivo. Second, by proteaome analysis, we observed that four proteins were highly oxidized in the gad mouse. We also demonstrated that UCH-L1 itself was oxidized and decreased its hydrolase activity as the oxidation increased. Third, we observed that UCH-L1 played some role in synaptic plasticity. Since UCH-L1 is selectively expressed in neurons, our results suggest that UCH-L1 may play an essential role in synaptic transmission.
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